title: Decreased expression of MBD2 and MBD4 gene and genomic-wide hypomethylation in patients with primary immune thrombocytopenia.
abstract: Genome-wide hypomethylation has been confirmed in patients with primary immune thrombocytopenia (ITP). Proteins containing methylcytosine-binding domain (MBD) are involved in promoter methylation as transcriptional repressors and promote the gene-silencing effect of DNA methylation. The purpose of this study was to investigate the methylation pattern of T cells and the relationship between genomic methylation and the expression of MBD2 and MBD4 in ITP patients. DNA deoxymethylcytosine content of CD4(+) cells from peripheral blood mononuclear cells was measured by enzyme-linked immunoassay. Real-time polymerase chain reaction was performed to quantify the transcription levels of MBD2 and MBD4 in peripheral blood mononuclear cells and CD4(+) cells. DNA dmC content in CD4(+) cells of ITP patients was significantly lower than in the controls (p = 0.001). The mRNA level of MBD2 and MBD4 in CD4(+) cells of ITP patients was statistically lower than those of the controls (p < 0.001). Positive correlations between methylation indexes and expression of each enzyme were observed in the control group (r(2) = 0.718, p = 0.004 for MBD2; r(2) = 0.608, p = 0.015 for MBD4). However, inverse correlations were found in ITP patients (r(2) = 0.604, p = 0.008 for MBD2; r(2) = 0.498, p = 0.027 for MBD4). Our results indicate that decreased expression of MBD2 and MBD4 might involve in the pathogenesis of ITP.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Zhen-ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: Dong-sheng
authors.initials: DS
authors.lastname: Gu
authors.forename: Ze-ping
authors.initials: ZP
authors.lastname: Zhou
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Chen
authors.forename: Zhen-xing
authors.initials: ZX
authors.lastname: Guo
authors.forename: Wei-ting
authors.initials: WT
authors.lastname: Du
authors.forename: Jing
authors.initials: J
authors.lastname: Ge
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: Ren-chi
authors.initials: RC
authors.lastname: Yang
mesh_terms: D000208:Acute Disease; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000235:genetics* / Q000503:physiopathology; D012313:RNA / Q000032:analysis*
chemical_list: D004268:DNA-Binding Proteins; C489325:MBD2 protein, human; D012313:RNA; D004706:Endodeoxyribonucleases; C118712:MBD4 protein, human